Quantifying association of early proteinuria and estimated glomerular filtration rate changes with long-term kidney failure in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis using the United Kingdom RaDaR Registry.

Abstract

C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN) are rare disorders that frequently result in kidney failure over the long-term. Presently, there are no disease-specific treatments approved for these disorders, although there is much interest in the therapeutic potential of complement inhibition. However, the limited duration and necessarily small size of controlled trials means there is a need to quantify how well short-term changes in estimated glomerular filtration rate (eGFR) and proteinuria predict the clinically important outcome of kidney failure. We address this using longitudinal data from the UK Registry of Rare Kidney Diseases (RaDaR) involving retrospective and prospective data collection with linkage to hospital laboratories via automated feeds of 371 patients. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression with eGFR slope estimated using linear mixed models. In a median of 11.0 (inter quartile range 7.4-15.1) years follow-up, 148 patients (40%) reached kidney failure. There was no significant difference in progression to kidney failure between C3G and IC-MPGN groups. Baseline urine protein-creatinine ratio (UPCR), although high, was not associated with kidney failure in either group. Two-year eGFR slope had a modest association with kidney failure. In contrast, both 20%‒50% and 50 mg/mmol reductions in UPCR between 0-12 months were associated with lower kidney failure risk in both groups. Notably, those with a UPCR under 100 mg/mmol at 12 months had a substantially lower risk of kidney failure (hazard ratio 0.10 (95% confidence interval 0.03-0.30). Overall, proteinuria a short time after diagnosis is strongly associated with long-term outcomes and a UPCR under 100 mg/mmol at one year is associated with a substantially lower kidney failure risk.